The present invention relates to the treatment of ailments in humans and other mammals, and more particularly, to a method and apparatus for delivering pharmaceutical compounds and genes into live cells of a patient.
It has long been known that it would be desirable to target certain cells within the body with specific pharmaceutical compounds. For example, in the treatment of certain types of cancer with chemotherapy it is necessary to use a high enough dose of a drug to kill the cancer cells without killing an unacceptably high number of normal cells. If the chemotherapy drug could be inserted directly inside the cancer cells, this objective could be achieved. However, some of the best anti-cancer drugs, for example, bleomycin, normally cannot penetrate the membranes of certain cancer cells.
Similarly, certain diseases could be treated by introducing desired genes into the specific cells of the patient. At present, most gene therapy experiments have utilized retroviruses as the carrier of the gene into the cells. When a retrovirus enters a target cell, it integrates essentially randomly in the genome and thus has the potential for introducing mutational damage by the mere fact of its insertion. If the virus integrates adjacent to an oncogene, malignant transformation of the target cell can result.
It is known that genes and other macromolecules such as pharmacological compounds can be incorporated into live cells through a process known as electroporation. The genes or other macromolecules are mixed with the live cells in a buffer medium and short pulses of high electric fields are applied. The cell membranes are transiently made porous and the genes or macromolecules enter the cells. There they can modify the genome of the cell.
The incorporation of drugs into red blood cells via electroporation as well as the incorporation of genes into white blood cells via electroporation have both been demonstrated. The selective incorporation of genes into white blood cells in whole blood via electroporation has also been demonstrated. The electroporation of cells in a flow-through apparatus has also been demonstrated. Recent methods of gene therapy have used variations of the procedures described above.
One therapeutic application of electroporation consists of the infusion of an anticancer drug and then electroporation of the drug into the tumor by applying voltage pulses between spaced electrodes. The voltage must be adjusted accurately so that the generated electrical field has the desired, optimal amplitude. With external, easily accessible tumors this can be done by applying the electrodes across the tumor, measuring the distance d between the electrodes and selecting the voltage V in the pulse generator so that the electric field E=V/d has the desired amplitude.
It would be desirable to have an automatic control system wherein the distance between electrodes applied to a tumor is automatically fed back to the control system to enable application of the desired voltage pulse.